Y Prado1, T Zambrano1, L A Salazar1. 1. Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La Frontera, Temuco, Chile.
Abstract
WHAT IS KNOWN AND OBJECTIVE: Statins are first-line therapy for reducing high cholesterol levels. However, response to these drugs shows high interindividual variability. We aimed to investigate the influence of two single nucleotide polymorphisms (SNP) (ABCB1 rs1128503 and ABCG2 rs2231142) in the ABC transporter genes on response to short-term low-dose atorvastatin in Chilean hypercholesterolaemic patients. METHODS: We studied 127 Chilean hypercholesterolaemic patients treated with 10 mg/d atorvastatin for 4 weeks. The lipid profile was determined before and after drug administration. Genotyping of the rs1128503 and rs2231142 variants was performed using TaqMan® Drug Metabolism Genotyping Assays. RESULTS AND DISCUSSION: Genotype distribution for all polymorphisms investigated was consistent with the Hardy-Weinberg equilibrium. Atorvastatin reduced TC, LDL-C and TG concentrations (P<.05), whereas HDL-C levels were found to be increased (P<.05). Minor allele frequencies for rs1128503 and rs2231142 variants were 0.453 and 0.075, respectively. In this study, patients prescribed with short-term low-dose atorvastatin and carrying ABCB1 (rs1128503) or ABCG2 (rs2231142) SNPs did not show differences in LDL-C response (P>.05). WHAT IS NEW AND CONCLUSION: The ABCB1 SNP was not associated with response to atorvastatin in Chilean subjects. The few ABCG2 421A homozygotes did not allow meaningful inferences to be made for this polymorphism.
WHAT IS KNOWN AND OBJECTIVE: Statins are first-line therapy for reducing high cholesterol levels. However, response to these drugs shows high interindividual variability. We aimed to investigate the influence of two single nucleotide polymorphisms (SNP) (ABCB1rs1128503 and ABCG2rs2231142) in the ABC transporter genes on response to short-term low-dose atorvastatin in Chilean hypercholesterolaemic patients. METHODS: We studied 127 Chilean hypercholesterolaemic patients treated with 10 mg/d atorvastatin for 4 weeks. The lipid profile was determined before and after drug administration. Genotyping of the rs1128503 and rs2231142 variants was performed using TaqMan® Drug Metabolism Genotyping Assays. RESULTS AND DISCUSSION: Genotype distribution for all polymorphisms investigated was consistent with the Hardy-Weinberg equilibrium. Atorvastatin reduced TC, LDL-C and TG concentrations (P<.05), whereas HDL-C levels were found to be increased (P<.05). Minor allele frequencies for rs1128503 and rs2231142 variants were 0.453 and 0.075, respectively. In this study, patients prescribed with short-term low-dose atorvastatin and carrying ABCB1 (rs1128503) or ABCG2 (rs2231142) SNPs did not show differences in LDL-C response (P>.05). WHAT IS NEW AND CONCLUSION: The ABCB1 SNP was not associated with response to atorvastatin in Chilean subjects. The few ABCG2 421A homozygotes did not allow meaningful inferences to be made for this polymorphism.